Different patterns of parasympathetic activation in uni- and bilateral migraineurs

Abstract

Several lines of evidence support involvement of the parasympathetic system in migraine: (i) migraine-associated symptoms, such as exaggerated facial flushing, lacrimation and rhinorrhea; (ii) increased levels of cranial venous vasoactive intestinal peptide in migraineurs during attacks; and (iii) reports of migraine pain alleviation by intranasal instillation of lidocaine, which can block some of the parasympathetic outflow to the cranium. This study assessed cranial parasympathetic function in migraineurs in between attacks, assuming that abnormal function might imply involvement of the parasympathetics in migraine pathogenesis. We tested 39 female migraineurs outside attacks, of whom 11 had bilateral pain, 20 unilateral at a specific side and eight alternating unilateral head pain, and 16 controls. The trigemino-parasympathetic reflex was studied, using soapy and saline eye drops for stimulation of the afferent limb of the reflex arch, and cutaneous vascular response at the forehead for the efferent limb. The latter was recorded by photoplethysmography on both sides of the forehead. We found no difference in vasodilatation between migraineurs as a group and controls (83.7 +/- 6.5% and 80.8 +/- 7.6%, respectively, not significant). However, when analysing data by the site of pain, we found that those with bilateral pain had the largest vasodilatation response (141.6 +/- 16.2%, P < 0.05 versus controls, analysis of varance, post hoc Tukey-Kramer HSD), while those with unilateral pain had the least vasodilatation (45.5 +/- 3.3%, P < 0.05). The response of patients with alternating pain (97.2 +/- 12.6%) did not differ from controls. It is concluded that cranial parasympathetic function does differ among patients with various migraine types at rest. Based on the understanding of dysfunctional brainstem pain modulation in migraine, we suggest a model of within-brainstem interaction between the two locus coeruleus nuclei, which are involved in control of pain and cranial parasympathetic outflow. The model assumes various levels of inhibitory inter-relationships between these two nuclei; diminution or absence of the normal reciprocal inhibitory relationships between them may underlie the augmented cranial parasympathetic response in bilateral migraineurs, while an excess of reciprocal inhibitory relationship between them may underlie the diminished cranial parasympathetic response in unilateral migraineurs. These findings might help in clarifying inter-relationships between brainstem nuclei in the context of migraine pathogenesis.

Migraine and neuropeptides

“…This statement is supported clinically by the finding that roughly 30% of migraine patients develop cranial autonomic parasympathetic symptoms such as lacrimation, rhinorrhoea and eyelid oedema (Avnon et al, 2003(Avnon et al, , 2004Barbanti et al, 2002;Gupta and Bhatia, 2007;Obermann et al, 2007). Immunohistological findings have revealed CGRP-ir nerve fibres in the SPG, CLR immunoreactivity in the SGCs and RAMP-1 immunoreactivity in the neurons and SGCs in the SPG (Csati et al, 2012b).…”

Errors in Recognition and Management are Still Frequent in Patients with Cluster Headache

“…The very different temporal patterns and duration of attacks in migraine and CH are key factors on distinguishing between these two conditions, as it is true that other features of these headaches can overlap. These overlapping features include the development of aura (known to occur in up to 20% of CH cases) [14], the pain intensity (2/3 of migraine patients also have severe pain), the existence of cranial autonomic symptoms (at least one of these symptoms is known to occur in about half of migraine patients) [15,16,17,18,19,20,21,22] or the presence of associated ‘migraine' features in CH attacks (in a large German cohort CH attacks associated photo/phonofobia in 61% and nausea and vomiting in 28% of cases) [13]. The IHS criteria of ‘strictly unilateral pain' may also cause confusion as switching attack sides has been reported in at least 10% of CH cases [23] and also in up to 10% of cases migraine attacks are strictly unilateral for years [24].…”

Functional brain imaging in hemicrania continua: Implications for nosology and pathophysiology

“…There is considerable experimental animal literature to document that stimulation of trigeminal afferents can result in cranial autonomic outflow, the trigeminal-autonomic reflex [51•]. In fact, some degree of cranial autonomic symptomatology is a normal physiologic response to cranial nociceptive input [52,53•] and patients with other headache syndromes may report these symptoms [54][55][56]. The distinction between these and other headache syndromes is the degree of cranial autonomic activation.…”